Field of the Invention
The current invention is in the field of nutrition and infant formulas for special purposes. More specifically, the invention is related to a composition for use as a feeding formula for children from 0 to 12 months old. Said formula has more tolerability and significantly decreases the adverse events produced by other formulas. More specifically, the composition of the invention is a new and improved food choice for children who exhibit symptoms of gastroesophageal reflux, abdominal colic and/or constipation.
Background Art
It is well known that the best way of feeding a newborn or an infant is by administering the milk of his own mother. In many cases this is not possible for many reasons, mainly because of the job activity of the mother or due to a physiological impairment that do not allow breast feeding. In these cases, the baby should be fed with a formula made from cow's milk. According to the National Nutrition Survey (2006), about 75% of the infants younger than four months were breastfed partly or fully with breast milk substitutes or infant formula. Generally, these formulas are well tolerated, but about 4 to 5% of the children in the first year of life according with some authors (Bock S A. Prospective appraisal of complaints of adverse Reactions to foods in children during the first three years of life. Pediatric 1987; 79:683-688.), or about 2 to 5% according with other authors (Host A, Halken S A. A prospective study of cow's milk allergy in Danish infants during the first Three years of life. Clinical course in relation to clinical and immunological type of hypersensitivity reaction. Allergy 1990, 45:587-596; Schrander J J P, Van Den Bogart J P H, Forget P P et al. Cow's milk protein intolerance in infants under 1 year of age: a prospective epidemiological study. Eur J Pediatr 1993; 152: 640-644), experience some form of gastrointestinal disorder with the use of these formulas. Infants consuming these formulas may suffer decreased appetite and/or regurgitation; additionally, changes in the natural process of gastric emptying, colic and intolerance to the formula components may occur.
One of these high prevalence disorders especially in children under 1 year of age is gastroesophageal reflux or regurgitation. Regurgitation occurs when gastric content escapes from the stomach into the upper digestive tract moving in the opposite direction to normal movement of food. Some authors report a high incidence of reflux reaching values of 67% among children under 4 months old. The figures may vary since the diagnosis of the disease involves the perception of the parents. In Mexico, data from the Mexican Academy of Pediatrics suggests that this condition occurs in 40% of children during the first months of life resulting in most of the cases in charges to families for healthcare.
Gastroesophageal reflux is common in newborns due to some factors such as gastrointestinal immaturity, high consumption of milk and inappropriate body postures. Gastroesophageal reflux is the cause of high morbidity, prolonged stays in hospital and has been associated with other disorders such as apnea, worsening of chronic diseases and other complications such as aspiration of gastric contents and oesophagitis (Corvaglia, L., Rotatori, R., Ferlini, M., Aceti, Ancora, G., Faldella, G. The effect of body positioning on gastroesophageal reflux in premature infants: evaluation by combined impedance and pH monitoring, J Pediatr 2007; 151: 691-6). An inadequate treatment exposes the child to undergo more regurgitation, resulting in more serious clinical manifestations, among them failure to thrive, recurrent respiratory infections and sometimes other life threatening events.
For preterm infants with oesophageal reflux, the treatment initially includes conservative interventions, related to body position. Also anti-reflux medications such as histamine receptor blockers-2 (H2) are commonly used during hospitalization and after discharge. However, clinical evidence has shown that the administration of these drugs increase the risk of necrotizing enterocolitis as well as the risk of an eventual sepsis (Guillet, R., Stoll, B J., Cotton, C M, et al. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics 2006 117: e137-42). Other drugs such as metoclopramide cause serious adverse effects including irritability of digestive tract, diastonic reactions, vomiting, emesis, and apnea.
Since the volume, osmolarity, caloric density, viscosity, nutrient content and the digestibility of the food may influence the appearance or disappearance of reflux events, the use of an appropriate diet is the main form of intervention and treatment of the gastroesophageal reflux disease. There is evidence in the literature that intervention with an appropriate diet without the use of drugs is effective to reduce reflux in infants (Shalaby T M, Orenstein S R. Efficacy of conservative therapy in infants with gastroesophageal reflux disease referred by pediatricians to pediatric gastroenterologists. Gastroenterology. 2001; 120:A49).
The most effective option to treat this condition is the use of infant formula with thickeners which increase viscosity. Some agents such as locust bean gum, carboxymethylcellulose, and compounds containing pectin and cellulose have been used with this objective, however, there is a high risk of decreasing the bioavailability of some nutrients with the use of these compounds.
Infant formulas recommended for infants with gastro-esophageal reflux are found in the prior art, some of which are described below:
Masson (U.S. Pat. No. 5,192,577) describes the use of xanthan gum in nutritional formulations; restricting its application to a stabilizer, but does not focus on solving intolerance problems.
Anfinone et al. (U.S. Pat. No. 5,681,600) describes the use of xanthan gum in a nutritional formula, however the use of this gum is considered inadequate due to the observation of a limited absorption of calcium.
Mahmoud (U.S. Pat. No. 4,670,268) describes the use of a hypoallergenic nutritional formula which may contain xanthan gum as a stabilizer. Nevertheless the patent does not claim the effective amount of xanthan gum used to produce an increase in viscosity.
There are in the market some formulas for children with regurgitation problems which incorporate gums as thickening agents, such us Nutrilon AR, Blemil Plus 1 and 2 AR; Nutriben 1 and 2 AR, and Enfalac 1 and 2 AR.
Borshel et al. (U.S. Pat. No. 6,365,218 B1) suggests a significant improvement in these formulas, through the addition of vitamins and minerals to compensate for the loss of these elements that take place with the use of xanthan gum.
Some formulations have used rice starch as a thickening agent, which contains from 17-24% amylose and 76-83% amylopectin. Amylopectin is less digestible than amylose, therefore formulas containing corn starch and/or rice starch will be less digestible due to high concentration of amylopectin. Potato starch, which belongs to the amilacias family possess higher concentration of amylose (from 50 to 70%) and less content of amylopectin (from 50 and 30%), therefore, a better tolerance results with the use of this starch. Some authors have replaced the use of rice starch or corn starch for potato starch (Martinez, U.S. Pat. No. 6,099,871).
Most studies focused on reducing regurgitation in infants have used viscosity-increasing agents, however, few of them have evaluated the impact of lactose reduction. Only Lasekan et al. (US Published Application 2003/0165606 A1) has proposed that a reduction of 70% or less in lactose levels of a total carbohydrates in infant formulas, may relieve regurgitation events that occur within the first months of life.
Besides the use of thickeners, other modifications such as increasing the casein content have been proposed as an option to relieve regurgitation events. This approach is due to the ability of casein to increase the density of rennet, reducing regurgitation but it delays gastric emptying, which can lead to constipation problems.
During reflux episodes, some other alterations occur simultaneously, such as stomach pain or colic and constipation; however, with the infant formulas developed to date it is not possible to treat all these problems simultaneously.
Colic is a common problem in childhood. Numerous reports in the pediatric literature suggest that this condition occurs between 10 and 30% of formula-fed infants. Colic in infants is detected by the presence of unexpected episodes of crying and whining which occur mainly at night. Despite the high incidence of colic and the vast amount of investigation that has been developed in this regard, its etiology has not been clearly elucidated. There is considerable evidence suggesting that colic is related to some type of food allergy and sometimes is the first manifestation of atopic dermatitis, however this correlation has not been fully elucidated (Schrander J J P, Van Den Bogart J P H, Forget P P et als. Cow's milk protein intolerance in infants under 1 year of age: a prospective epidemiological study. Eur J Pediatr 1993; 152: 640-644; Hill, D, and Hosking, C S. Infantile colic and food hypersensitivity. Journal of Pediatric Gastroenterology 2000; 30 (1): s67-s76). For cases where it is believed that colic is related to allergy to intact protein, formulas based on partially or extensively hydrolyzed protein have been developed (Jakobsson I, Lothe L, Ley D, Borschel M W. Effectiveness of cassein hydrolysates feedings in infants with colic. Acta Pediatr 2000; 89: 18-21; Lucassen, P L J B, Assendelt, W J J, Gubbels J W, van Eijk J T M, Douwes A C. Infantile colic:crying time reduction with a whey hydrolysate: a double-blind, randomized, placebo-controlled trial. Pediatrics 2000; 106: 1349-1354). Many cases of colic are related to food allergy, but not all of them, that is why, intervention is much more complex than just replacing milk protein by protein hydrolyzates.
Other modifications are addressed to mitigate the potential factors triggering colic, among those are the reduction of lactose content, contribution of oligosaccharides to achieve prebiotic effect and the inclusion of higher percentage of lipids with palmitic acid attached to the beta carbon of glycerol molecule (beta palmitic acid).
Savino et al. (Savino F, Palaumeri E, Castagno E, Cresi F, Dalmasso P, Cavallo F, Oggero R. Reduction of crying episodes owing to infantile colic: a randomized controlled study on the efficacy of a new infant formula. European Journal of Clinical Nutrition 2006; 60: 1304-1310), evaluated the efficacy of an infant formula on the reduction of crying episodes related to infantile colic. This formula consisted of partially hydrolyzed whey proteins, oligosaccharides with prebiotic effect and high proportion of beta palmitic acid. The formula significantly reduced the episodes of crying compared to the standard formula. However, the formula lacks other nutrients commonly found in breast milk and essential for the proper development of children, such as docosahexaenoic acid (DHA), arachidonic acid (ARA), inositol, choline, taurine and carnitine, among others.
Other strategies found in the literature addressed to remedy colic events is the use of infant formula with a source of fiber and protein hydrolyzates, as described by Borschel et al. in the U.S. Pat. No. 5,021,245; however, its use in children under 6 months is questionable since it is until 6 months of age when solid foods such as cereals, fruits and vegetables containing fiber, are included into the infant diet.
Constipation is defined as the difficulty presented by the baby to remove stool from the body, when this happens, the feces are accumulated in the intestines. The delay in the intestines movement extends the time feces remain in them. Therefore, this causes that the body may reabsorb the liquid contained in stools, turning feces drier and harder leading to more constipation.
The main cause of constipation in lactants are the dietary modifications such as the change from breastfeeding to infant formula; changes of infant formula or the inadequate preparation of formulas by dissolving improper quantities of powder, among others. It has been suggested that the change from breastfeeding to the introduction of other foods, plays an important role in the onset of symptoms of constipation in childhood, however the mechanisms involved are unknown.
Constipation in children fed with infant formula, may be the result of the presence of calcium soaps in the stool, which hardly occurs in breastfed children. Lipids of breast milk have a 70% of palmitic acid attached to the beta carbon of the glycerol molecule, higher than those usually found in infant formulas currently used.
Palmitic acid attached to the alpha carbon of the glycerol molecule remain released in the intestine, bind to calcium molecule and precipitate, thus they are not absorbed but they also harden the stools. The addition of lipids with beta palmitic acid makes softer stool and promote the absorption of lipids and divalent metals such as magnesium and calcium. Other potential modifications that favor the treatment of constipation include the addition of oligosaccharides, supplementation with long chain fatty acids and the addition of partially hydrolyzed protein.
Infant formulas with one or more of the aforementioned characteristics are commercially available, that help relieve constipation. Within them we can mention Blemil Plus 1 and 2, Novalac AE, Nutriben 1 and 2, and Sanutri 1 and 2.
Bindels et al. (U.S. Pat. No. 6,863,918 B2) describe an improved infant formula, which reduces constipation and gastrointestinal disorders. That formula is composed by prebiotics, a viscosity modifying agent, also a portion of protein hydrolysates, preferably from serum. Additionally, the formula contains at least one easy-digestible lipid component and at least one endo or exo proteinase. However, the composition of such patent it is limited in terms of content of other nutrients essential for the proper development of children. Moreover, this formulation does not contain potato starch as a thickening agent, so it does not produce the benefits that its inclusion represents.
On the other hand, research aimed to develop infant formulas has been focused in obtaining a protein profile similar to the one found in breast milk, mainly the whey fraction, in order to reduce adverse events.
In this respect, Kuhlman et al. in U.S. Pat. No. 6,913,778 B2, disclosed an infant formula on which protein is obtained from whey, which 40% or less of the total protein is alpha-lactalbumin and 8% is beta-lactoglobulin. On the other hand, Davis and Kuhlman (US Published Application No. 2005/0142249 A1), describe a method for reducing the side effects observed when infants are fed with infant formula. Said method consists in administering a composition where cow's milk provides between 1.0 and 1.2 grams of protein per 100 kcal, plus a certain amount of whey that provides between 1.0 and 1.2 grams of protein per 100 kcal. The whey used in such formulation contains from 28 to 40% of alpha-lactoalbumin and from 8 to 33% of beta-lactoglobulin. These formulas have been successful in decreasing adverse events associated with the consumption of milk formulas, although they are deficient in some other components necessary to reduce colic and reflux episodes, such as thickening agents, prebiotics, lipids with palmitic acid in the beta position, and other components essential for a proper development such as DHA and ARA.
The developments in the area of infant formulas performed to date are plenty but there is no formula or method of treatment that optimally reduces gastro-esophageal reflux, colic and constipation, symptoms that usually occur simultaneously in the newborns. The invention described below describes a novel infant formula for the simultaneous treatment of these three conditions.